The objective of this reserach is to identify the mechanisms of total body clearance of volatile halogenated anesthetics and their metabolites in man. By measuring the absorbed dose of drug during clinical anesthesia and the amount exhaled and excreted as urinary metabolities, we have shown that the larger the fraction of dose excreted as urinary metabolites, the larger the fraction which cannot be accounted for by these methods. We proposed to extend these balance studies to include halothane and sevoflurane, a promising new drug that is resistant to biotransformation. The influence of chronic ingestion of anticonvulsant drugs on the uptake, elimination and extent of biotransformation of halothane and enflurane will be determined. Methods for estimating the extent of tissue binding of metabolites will be applied to human tissues obtained at autopsy. Separation and measurement of urinary metabolites following halothane anesthesia will be pursued in an effort to determine extent of conjugation of halothane metabolites in man. The kinetics of drug metabolism of inhalation anesthetics will be studied in the monkey.